Targeting SMN to Cajal bodies and nuclear gems during neuritogenesis

Chromosoma. 2004 Jun;112(8):398-409. doi: 10.1007/s00412-004-0285-5. Epub 2004 May 25.

Abstract

Neurite outgrowth is a central feature of neuronal differentiation. PC12 cells are a good model system for studying the peripheral nervous system and the outgrowth of neurites. In addition to the dramatic changes observed in the cytoplasm, neuronal differentiation is also accompanied by striking changes in nuclear morphology. The large and sustained increase in nuclear transcription during neuronal differentiation requires synthesis of a large number of factors involved in pre-mRNA processing. We show that the number and composition of the nuclear subdomains called Cajal bodies and gems changes during the course of N-ras-induced neuritogenesis in the PC12-derived cell line UR61. The Cajal bodies found in undifferentiated cells are largely devoid of the survival of motor neurons (SMN) protein product. As cells shift to a differentiated state, SMN is not only globally upregulated, but is progressively recruited to Cajal bodies. Additional SMN foci (also known as Gemini bodies, gems) can also be detected. Using dual-immunogold labeling electron microscopy and mouse embryonic fibroblasts lacking the coilin protein, we show that gems clearly represent a distinct category of nuclear body.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Cell Differentiation
  • Cell Nucleus / chemistry*
  • Coiled Bodies / chemistry*
  • Cyclic AMP Response Element-Binding Protein
  • Cytoplasm
  • Dexamethasone / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Fibroblasts / metabolism
  • Humans
  • Methyltransferases / antagonists & inhibitors
  • Mice
  • Microscopy, Electron
  • Motor Neurons
  • Muscular Atrophy, Spinal
  • Nerve Tissue Proteins / genetics*
  • Neurites / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • RNA-Binding Proteins
  • SMN Complex Proteins

Substances

  • Anti-Inflammatory Agents
  • Cyclic AMP Response Element-Binding Protein
  • Enzyme Inhibitors
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • RNA-Binding Proteins
  • SMN Complex Proteins
  • p80-coilin
  • Dexamethasone
  • Methyltransferases